DOT1L modulates the senescence-associated secretory phenotype through epigenetic regulation of IL1A

Oncogene-induced senescence (OIS) is a stable cell cycle arrest that occurs in normal cells upon oncogene activation. Cells undergoing OIS express a wide variety of secreted factors that affect the senescent microenvironment termed the senescence-associated secretory phenotype (SASP), which is beneficial or detrimental in a context-dependent manner. OIS cells are also characterized by marked epigenetic changes. We globally assessed histone modifications of OIS cells and discovered an increase in the active histone marks H3K79me2/3. The H3K79 methyltransferase disruptor of telomeric silencing 1-like (DOT1L) was necessary and sufficient for increased H3K79me2/3 occupancy at the IL1A gene locus, but not other SASP genes, and was downstream of STING. Modulating DOT1L expression did not affect the cell cycle arrest. Together, our studies establish DOT1L as an epigenetic regulator of the SASP, whose expression is uncoupled from the senescence-associated cell cycle arrest, providing a potential strategy to inhibit the negative side effects of senescence while maintaining the beneficial inhibition of proliferation.     

Psychological processes mediating the association between developmental trauma and specific psychotic symptoms in adults: a systematic review and meta‐analysis

Experiencing psychological trauma during childhood and/or adolescence is associated with an increased risk of psychosis in adulthood. However, we lack a clear knowledge of how developmental trauma induces vulnerability to psychotic symptoms. Understanding the psychological processes involved in this association is crucial to the development of preventive interventions and improved treatments. We sought to systematically review the literature and combine findings using meta‐analytic techniques to establish the potential roles of psychological processes in the associations between developmental trauma and specific psychotic experiences (i.e., hallucinations, delusions and paranoia). Twenty‐two studies met our inclusion criteria. We found mediating roles of dissociation, emotional dysregulation and post‐traumatic stress disorder (PTSD) symptoms (avoidance, numbing and hyperarousal) between developmental trauma and hallucinations. There was also evidence of a mediating role of negative schemata, i.e. mental constructs of meanings, between developmental trauma and delusions as well as paranoia. Many studies to date have been of poor quality, and the field is limited by mostly cross‐sectional research. Our findings suggest that there may be distinct psy­chological pathways from developmental trauma to psychotic phenomena in adulthood. Clinicians should carefully ask people with psychosis about their history of developmental trauma, and screen patients with such a history for dissociation, emotional dysregulation and PTSD symptoms. Well conducted research with prospective designs, including neurocognitive assessment, is required in order to fully understand the biopsychosocial mechanisms underlying the association between developmental trauma and psychosis.     

Primate Location Preference in a Double-Tier Cage: The Effects of Illumination and Cage Height

Nonhuman primates are frequently housed in double-tier arrangements with significant differences between the environments of the upper and lower-row cages. Although several studies have investigated whether this arrangement alters monkeys' behavior, no studies have addressed the two most notable differences, light and height, individually to determine their relative importance. This experiment examined how rhesus and long-tailed macaques allocated their time between the upper and lower-row cages of a 1-over-1 apartment module under different lighting conditions. In Condition A, monkeys' baseline degree of preference for the upper- and lower-row was tested. In Condition B, the lighting environment was reversed by limiting illumination in the upper-row cage and increasing illumination in the lower-row cage. In both conditions, monkeys spent more time in the upper-row cage, thus indicating a strong preference for elevation regardless of illumination. The amount of time that monkeys spent in the lower-row cage increased by 7% under reversed lighting, but this trend was not significant. These results corroborate the importance of providing captive primates with access to elevated areas.     

Synthesis of Reagents for Fluorescence-Tagging of DNA

Abstract

A general route for the synthesis of alkynylamino nucleoside triphosphates is described. These nucleosides can be selectively coupled through the alkynylamino group to a variety of reporter groups and used to enzymatically label DNA.     

Does rearing an aphid parasitoid on one host affect its ability to parasitize another species?

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